FDFT1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: Squalene synthase is a C-terminally anchored endoplasmic reticulum membrane protein; the phylogenetic IBA correctly places its active enzymatic location at the ER membrane. Reason: UniProt records the subcellular location as the endoplasmic reticulum membrane (multi-pass), consistent with the family-wide phylogenetic inference. This is a core aspect of the gene's biology. Supporting Evidence: file:human/FDFT1/FDFT1-uniprot.txt Endoplasmic reticulum membrane file:human/FDFT1/FDFT1-uniprot.txt Multi-pass membrane protein
GO:0051996 squalene synthase [NAD(P)H] activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function. FDFT1 is squalene synthase, catalysing the NAD(P)H-dependent condensation of two farnesyl diphosphate molecules to squalene (EC 2.5.1.21). Reason: The IBA is fully supported by experimental characterization of the human enzyme, including the crystal structure and catalytic assays. This is the defining core function of the gene. Supporting Evidence: PMID:10896663 through a reductive dimerization of two farnesyl diphosphate (FPP) file:human/FDFT1/FDFT1-uniprot.txt Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP)
GO:0006695 cholesterol biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Squalene synthase catalyses the first committed step toward cholesterol; its product squalene is cyclised (via lanosterol) to cholesterol. Reason: Well supported: FPP conversion to squalene by SQS is the first committed step in cholesterol formation, and the human enzyme functionally complements sterol-deficient yeast. This is a core biological process for the gene. Supporting Evidence: PMID:10896663 squalene synthase represents the first committed PMID:10896663 Squalene synthase catalyzes the biosynthesis of squalene, a key
GO:0045338 farnesyl diphosphate metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: FPP is the substrate of squalene synthase; the enzyme consumes two FPP molecules per catalytic cycle, so it participates in farnesyl diphosphate metabolism. Reason: Accurate: SQS is the enzyme that diverts FPP into the sterol branch, and FPP sits at the branch point of the isoprenoid pathway. This is correct though secondary to the squalene synthase activity/cholesterol biosynthesis annotations. Supporting Evidence: PMID:10896663 the final branch point in the isoprenoid biosynthesis pathway file:human/FDFT1/FDFT1-uniprot.txt Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP)
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000117	ACCEPT	Summary: Localizes to the endoplasmic reticulum. Correct but less precise than the ER membrane annotation. Reason: Consistent with the UniProt ER membrane subcellular location and with the IDA HPA immunofluorescence annotation to the ER. ER is a valid (broader) location. Supporting Evidence: file:human/FDFT1/FDFT1-uniprot.txt Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: ER membrane localization, mapped from the UniProt subcellular location keyword. Reason: Matches the curated UniProt subcellular location; SQS is a multi-pass ER membrane protein. Core localization. Supporting Evidence: file:human/FDFT1/FDFT1-uniprot.txt Endoplasmic reticulum membrane
GO:0006694 steroid biosynthetic process	IEA GO_REF:0000117	ACCEPT	Summary: Broad parent term covering sterol/cholesterol biosynthesis. True but less specific than cholesterol biosynthetic process. Reason: Correct as a broader classification of the gene's role in sterol/cholesterol synthesis; retained but not the most informative BP term (see GO:0006695). Supporting Evidence: file:human/FDFT1/FDFT1-uniprot.txt It is the first committed enzyme of the sterol biosynthesis pathway
GO:0008610 lipid biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: Very general parent term (sterols are lipids). True but uninformative relative to the cholesterol/sterol biosynthesis annotations. Reason: Not incorrect: cholesterol biosynthesis is a lipid biosynthetic process. Retained as a high-level classification; the more specific terms carry the biology. Supporting Evidence: file:human/FDFT1/FDFT1-uniprot.txt It is the first committed enzyme of the sterol biosynthesis pathway
GO:0016020 membrane	IEA GO_REF:0000117	ACCEPT	Summary: Generic membrane localization; SQS is a multi-pass membrane protein. Correct but far less specific than endoplasmic reticulum membrane. Reason: True but a high-level parent of the ER membrane annotation. Retained; the ER membrane term is the informative one. Supporting Evidence: file:human/FDFT1/FDFT1-uniprot.txt Multi-pass membrane protein
GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups	IEA GO_REF:0000002	ACCEPT	Summary: Parent MF term corresponding to EC 2.5.1.- (alkyl/aryl transferases); squalene synthase (EC 2.5.1.21) is a member. Correct but general. Reason: An InterPro2GO mapping to the correct enzymatic superclass. It is accurate but subsumed by the specific squalene synthase [NAD(P)H] activity term (GO:0051996). Supporting Evidence: file:human/FDFT1/FDFT1-uniprot.txt EC=2.5.1.21
GO:0045338 farnesyl diphosphate metabolic process	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based duplicate of the IBA farnesyl diphosphate metabolic process annotation; FPP is the substrate of SQS. Reason: Correct; consistent with the IBA annotation to the same term. SQS consumes FPP. Supporting Evidence: file:human/FDFT1/FDFT1-uniprot.txt Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP)
GO:0051996 squalene synthase [NAD(P)H] activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated (RHEA/EC 2.5.1.21) mapping to the core squalene synthase activity. Duplicate of the experimentally-supported EXP/IBA annotations. Reason: Correctly recapitulates the core molecular function from RHEA:32295/32299 and EC 2.5.1.21. Supporting Evidence: file:human/FDFT1/FDFT1-uniprot.txt EC=2.5.1.21
GO:0005515 protein binding	IPI PMID:23864651 The identification of novel proteins that interact with the ...	MARK AS OVER ANNOTATED	Summary: FDFT1/SQS was identified as one of many candidate interactors of the GLP-1 receptor in a membrane split-ubiquitin yeast two-hybrid / CO-IP screen. This is a generic protein-binding annotation with no specific molecular function attached. Reason: Bare protein binding (GO:0005515) is uninformative and, here, derives from a high-throughput GLP-1R interactome screen in which SQS is a co-detected membrane partner; it does not describe the enzyme's function. Per curation policy, marked as over-annotated rather than removed. Supporting Evidence: PMID:23864651 identify proteins that interact with the GLP-1R
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: Protein-binding annotation arising from an interactome-scale edgotyping study of Mendelian disease alleles. Generic and uninformative for FDFT1 molecular function. Reason: Bare protein binding from a systematic interaction-perturbation dataset; no specific binding partner/function is established for SQS beyond an entry in a large interaction map. Marked as over-annotated per policy (not removed). Supporting Evidence: PMID:25910212 two-thirds of disease-associated alleles perturb protein-protein
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Multiple binary interactions for FDFT1 from HuRI (human reference interactome, Y2H). Many partners are ER/membrane proteins, consistent with an ER-membrane enzyme, but no specific molecular function is defined by these bare protein-binding calls. Reason: Bare protein binding (GO:0005515) from a proteome-scale binary interactome; uninformative regarding SQS function. Marked as over-annotated rather than removed, per curation policy. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions
GO:0005783 endoplasmic reticulum	IDA GO_REF:0000052	ACCEPT	Summary: Direct immunofluorescence (Human Protein Atlas) localizes FDFT1 to the endoplasmic reticulum. Reason: Experimental (IDA) localization consistent with the curated ER membrane subcellular location. Supports the core ER localization. Supporting Evidence: file:human/FDFT1/FDFT1-uniprot.txt Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	ISS GO_REF:0000024	ACCEPT	Summary: ER membrane localization inferred by sequence similarity to an ortholog (UniProtKB:Q02769, rat SQS). Consistent with all other localization evidence. Reason: Curator-judged sequence-similarity transfer of the ER membrane location; agrees with the IBA, IDA (ER), TAS (Reactome), and IEA annotations. Core localization. Supporting Evidence: file:human/FDFT1/FDFT1-uniprot.txt Endoplasmic reticulum membrane
GO:0051996 squalene synthase [NAD(P)H] activity	EXP PMID:10896663 Crystal structure of human squalene synthase. A key enzyme i...	ACCEPT	Summary: Experimental determination of squalene synthase catalytic activity on the human enzyme, accompanying its crystal structure: reductive dimerization of two FPP molecules to squalene. Reason: Direct experimental support (EXP) for the defining molecular function from the human SQS crystal-structure/catalysis study. This is the anchor experimental annotation for the core function. Supporting Evidence: PMID:10896663 through a reductive dimerization of two farnesyl diphosphate (FPP) PMID:10896663 Squalene synthase catalyzes the biosynthesis of squalene, a key
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-1655850	ACCEPT	Summary: Reactome (FDFT1 expression event) places the enzyme at the ER membrane. Consistent with all other localization evidence. Reason: Traceable author statement from Reactome agreeing with the curated ER membrane location. Supporting Evidence: Reactome:R-HSA-1655850 The FDFT1 gene is transcribed to yield mRNA
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-191402	ACCEPT	Summary: Reactome reaction (reduction of presqualene diphosphate to squalene) is annotated to the ER membrane, where SQS acts. Reason: Reactome TAS for the second half-reaction of squalene synthesis, consistent with the ER membrane localization of the enzyme. Supporting Evidence: Reactome:R-HSA-191402 catalyzes the reduction of presqualene diphosphate (PSQPP) to squalene
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-191405	ACCEPT	Summary: Reactome reaction (dimerization of two FPP molecules to presqualene diphosphate) at the ER membrane, catalysed by FDFT1. Reason: Reactome TAS for the first half-reaction of squalene synthesis, consistent with the ER membrane localization of the enzyme. Supporting Evidence: Reactome:R-HSA-191405 catalyzes the reductive dimerization of two farnesyl diphosphate (FAPP) molecules to form
GO:0006694 steroid biosynthetic process	TAS PMID:8474436 Conservation between human and fungal squalene synthetases: ...	ACCEPT	Summary: SQS is a major control point of sterol biosynthesis; human/yeast/fungal enzymes are conserved and the human enzyme rescues sterol-deficient yeast. Steroid (sterol) biosynthesis is a broad but accurate BP. Reason: Traceable author statement supported by demonstrated conservation and functional complementation. Correct though broader than the cholesterol biosynthetic process term. Supporting Evidence: PMID:8474436 is thought to represent a major control point PMID:8474436 reversed the ergosterol requirement of S.
GO:0016020 membrane	TAS PMID:8474436 Conservation between human and fungal squalene synthetases: ...	ACCEPT	Summary: SQS is predicted/shown to be a C-terminal membrane-spanning protein. Generic membrane term; the ER membrane annotations are more specific. Reason: Traceable author statement; correct that SQS is a membrane protein. Subsumed by the ER membrane annotations, which carry the informative localization. Supporting Evidence: PMID:8474436 C-terminal membrane-spanning proteins of approximately 50

Gene Description

Existing Annotations Review

Core Functions

Squalene synthase: catalyses the NAD(P)H- and Mg2+-dependent reductive condensation of two molecules of farnesyl diphosphate to squalene (via presqualene diphosphate), the first committed step of sterol biosynthesis, at the endoplasmic reticulum membrane.

References

📚 Additional Documentation

Notes

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